phylogenetic and phytochemical characteristics abstract klein

8/22/2019 Phylogenetic and Phytochemical Characteristics Abstract KLEIN

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PHYLOGENETIC AND PHYTOCHEMICAL CHARACTERISTICS

OF PLANT SPECIES WITH ADAPTOGENIC PROPERTIES

by

Roberta Ann Klein

A thesis submitted in partial fulfillment

of the requirements for the degree

of

Masters of Science

in

Plant Sciences and Plant Pathology

MONTANA STATE UNIVERSITYBozeman, Montana

May 2004


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IMPORTANT NOTE: This thesis document is not the original thesis. It has been reformatted for 10pt and

single spacing and does not include some of the extraneous front matter required by thesis publication. The

purpose is to shorten it and make it easier to download and more accessible.

OM A RA PA TSA NA DHI

vis medicatrix naturae

VITA

Roberta (Robyn) Ann Klein was born in Detroit, Michigan on May 15, 1954, the daughter of

Evangeline Marie (Rioux) Klein and Robert Francis Klein.

After completing a Bachelors Degree in Psychology at Central Michigan University in 1975, Robyn

worked as a drug abuse counselor in a community mental health clinic. She then traveled throughout the

United States becoming interested in medicinal plants and embarking on a twenty-year endeavor in the

study of plants for healing. She completed a course in herbalism at the Dominion Herbal College inBurnaby, British Columbia in April 1982. In the ensuing years, Robyn taught throughout the United States

at conferences and schools of herbalism, and published many articles for both popular and peer-reviewed

herbal publications. In 1995, she continued her herbal studies with the well-known Rocky Mountain

herbalist, Michael Moore, at the Southwest School of Botanical Medicine in Albuquerque, New Mexico.

Robyn later served as faculty at the Southwest School of Botanical Medicine (Bisbee, AZ); the Dominion

Herbal College (Burnaby, BC); the National School of Phytotherapy (Albuquerque, NM); and the Rocky

Mountain School of Botanical Studies (Boulder, CO). She was accepted as a professional member of the

American Herbalists Guild in 1991, the highest possible recognition of clinical herbalism skills in the

United States at that time. In 1999, Robyn served as chair of the Montana Governors Task Force on Wild

Medicinal Plants to study commercial harvesting activities of native plants in the state.

Thus, at the time of her acceptance into the Graduate Program at Montana State University in 2002,

Robyn was well versed in the discipline of herbal medicine and the bioactivity of plant compounds.

Acknowledgments

I am very grateful for the support and vision of my thesis advisor, Dr. Matt Lavin.

Humble gratitude is also offered to the invaluable members of my thesis committee, Dr. Florence V.

Dunkel, Dr. Cathy Cripps, and Dr. Rich Stout, for their assistance and for their faith in my somewhat avant-

garde project.

I must also acknowledge the behind the scenes, unflagging support of the staff and librarians of the

Renne Library. This thesis required access to hundreds of academic papers and a few somewhat obscureinterlibrary loans to which the staff was flawless in obtaining.

The nature of this project required some distant expertise. These professionals were both kind and

generous in their assistance. Of particular mention are Dr. Kelly Kindscher, University of Kansas; Dr.

Alexander G. Panossian, C. Guelbenkian Research and Drug Quality Control Laboratories, Armenia; Dr.

Karel Slama, Czech Academy of Sciences, Republic of Czechoslovakia; and my herbalist colleagues,

Richo Cech, Horizon Herbs, OR; Kevin Spelman, Tia Sophia Institute, MD; Terry Willard, Ph.D., Wild

Rose College of Natural Healing, Calgary, BC; David Winston, Herbalist & Alchemist, NJ; and Donnie

Yance, Center for Natural Healing, OR.


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TABLE OF CONTENTS

LIST OF TABLES ..................................................................................................................................x

LIST OF FIGURES ...............................................................................................................................xi

ABSTRACT ..........................................................................................................................................xii

1. INVESTIGATION ANDPROJECT OVERVIEW......................................................................1

INTRODUCTION...........................................................................................................................1

GOALS OF INVESTIGATION.....................................................................................................3

Methods and Materials.............................................................................................................4

SUMMARY.....................................................................................................................................5

2. DESCRIPTIVE SURVEY OF THE LITERATURE ...................................................................7

METHODS......................................................................................................................................7Complementary and Alternative Medicine...........................................................................11

Conventional Medicine..........................................................................................................11

Natural Products Research.....................................................................................................12Plant Science...........................................................................................................................13

Plant Systematics....................................................................................................................13

Human Nutrition.....................................................................................................................14

Pharmacology .........................................................................................................................14

Human Pathophysiology........................................................................................................14

Biochemistry and Molecular Biology ...................................................................................15

Entomology.............................................................................................................................16

Phytotherapy...........................................................................................................................16

Traditional Medicine and Ethnopharmacology ....................................................................16

Toxicology..............................................................................................................................18

SUMMARY...................................................................................................................................18

3. STRESS PHYSIOLOGY AND PATHOLOGY .........................................................................20

THE STRESS RESPONSE ..........................................................................................................20

Homeostasis and Allostasis ...................................................................................................22

Regulation of Stress ...............................................................................................................24

Allostatic Overload and Pathogenesis...................................................................................27

SUMMARY...................................................................................................................................30

4. ADAPTOGENIC STRESS REMEDIES.....................................................................................32

INTRODUCTION.........................................................................................................................32

TRADITIONAL MEDICINE ......................................................................................................32

ADAPTOGENS ............................................................................................................................35

Clarification of Definition .....................................................................................................37Analytical Methods ................................................................................................................42

Human Clinical Studies .........................................................................................................43

Non-Plant Adaptogens ...........................................................................................................44

Fungi.................................................................................................................................44

Shilajit ..............................................................................................................................45

Deer Antler ......................................................................................................................45

Safety of Dietary Supplements..............................................................................................46

SUMMARY...................................................................................................................................47


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5. PRELIMINARY SURVEY OF ETHNOBOTANICAL LITERATURE..................................50

INTRODUCTION.........................................................................................................................50

Methods...................................................................................................................................51

RESULTS......................................................................................................................................52

North American Ethnobotany Aspects .................................................................................56

SUMMARY...................................................................................................................................60

6. CHEMICAL COMPOUNDS OF ADAPTOGENIC SPECIES.................................................61

INTRODUCTION.........................................................................................................................61

TERPENOIDS...............................................................................................................................66

Triterpene Saponins ...............................................................................................................66

Phytosterols.............................................................................................................................70

Phytoecdysteroids...................................................................................................................74

PHENYLPROPANOIDS .............................................................................................................76

Flavonoids...............................................................................................................................77

Petal Color ......................................................................................................................79Lignans....................................................................................................................................81

OXYLIPINS AND FATTY ACIDS ............................................................................................82

POLYSACCHARIDES ................................................................................................................85CHEMOTAXONOMY.................................................................................................................86

SUMMARY...................................................................................................................................89

7. MECHANISM OF ACTIONS OF ADAPTOGENS ..................................................................91

INTRODUCTION.........................................................................................................................91

NEUROENDOCRINE ACTIVITY .............................................................................................92

Antioxidant Activity...............................................................................................................96

Nootropic Activity..................................................................................................................99

Nitric Oxide Activity............................................................................................................100

Aphrodisiac Activity ............................................................................................................103

HYDROXYLATION..................................................................................................................105

CELL MEMBRANE ACTIVITY..............................................................................................106HORMESIS .................................................................................................................................108

SYNERGISM ..............................................................................................................................111

SUMMARY.................................................................................................................................112

8. PHYLOGENETIC ANALYSIS.................................................................................................115

ADAPTOGENIC TRAIT OF PLANT SPECIES .....................................................................115Methods.................................................................................................................................117

MONOPHYLETIC CLADES....................................................................................................129

Trichopus in the Dioscoraceae ............................................................................................130

Trichopus sempervirens ...............................................................................................131

Trichopus zeylanicus....................................................................................................131

Epimedium in the Berberidaceae.........................................................................................132Epimedium brevicornu.................................................................................................134

Epimedium koreanum ..................................................................................................135

Epimedium saggitattum ...............................................................................................135

Rhodiola in the Crassulaceae...............................................................................................135Rhodiola rosea..............................................................................................................136Rhodiola sacra..............................................................................................................137Rhodiola sachalinensis ................................................................................................137

Astragalus and Glycyrrhiza in the Fabaceae ......................................................................137

Astragalus membranaceus andA. membranaceus varmongholicus ........................139


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Glycyrrhiza glabra .......................................................................................................140

Glycyrrhiza uralensis ...................................................................................................141

Hoppea in the Gentianaceae ................................................................................................141

Hoppea dichotoma andH. fastigiata ..........................................................................142

Panax in the Araliaceae .......................................................................................................142

Panax ginseng...............................................................................................................144Panax quinquefolium ...................................................................................................144

Codonopsis in the Campanulaceae......................................................................................144

Codonopsis lanceolata .................................................................................................145

Codonopsis pilosula .....................................................................................................146

Cardueae in the Asteraceae .................................................................................................146

Leuzea carthamoides ....................................................................................................147

Rhaponticum uniflorum ...............................................................................................148

Serratula coronata .......................................................................................................148

Discussion.............................................................................................................................148

PHYTOGEOGRAPHY ..............................................................................................................149

SUMMARY ................................................................................................................................154

LITERATURE CITED .......................................................................................................................156

APPENDICES.....................................................................................................................................184

APPENDIX A: LIST OF 183 SPECIES OF INTEREST ...............................................................185

APPENDIX B: LITERATURE SURVEYED .................................................................................188

APPENDIX C: PHARMACOLOGICAL EFFECTS OF ADAPTOGENS ON HUMANS AND

OTHER ANIMALS ............................................................................................................................195

APPENDIX D: HUMAN CLINICAL STUDIES............................................................................205

APPENDIX E: PLANT COMPOUNDS FOUND IN 33 ADAPTOGENIC SPECIES ................210


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LIST OF TABLES

Table Page

1. A listing of terms used to search for adaptogenic activity ........................................................... 8

2. Examples ofin vitro and in vivo experiments involving plant adaptogens

........................................................................................................................................................ 43

3. Potential adaptogens identified in ethnobotanical literature ...................................................... 53

4. Three classes of compounds associated with adaptogens and the biosynthetic pathways in plants........................................................................................................................................................ 62

5. Plant compounds believed to be responsible for adaptogenic effects and the plants containingthem................................................................................................................................................ 65

6. Petal color of adaptogen species from this investigation ........................................................... 80

7. Adaptogenic plant species and main chemical classes of compounds ...................................... 87

8. The essential methods employed to build a phylogenetic tree of angiospermspecies with and without the adaptogenic trait .........................................................................116

9. List of taxa applied to Phylomatic in formatted style...............................................................118

10. Monophyletic groups resulting from the phylogenetic tree (Figure 8) in which shared similarityof adaptogenic traits is due to inheritance from the most recent common ancestor ..............127

11. Major angiosperm orders with adaptogenic species ................................................................. 129

LIST OF FIGURES

Figure Page

1. Structure of plant oxylipins compared to human compounds ................................................... 83

2. Classes of compounds found in adaptogenic plants ................................................................... 93

3. Comparison of triterpenoids and cortisol .................................................................................... 93

4. Comparison of phenylpropanoids and catecholamines .............................................................. 94

5. Comparison of plant oxylipins and human leukotrienes ............................................................ 94

6. U-shaped dose-response curve...................................................................................................109

7. The Nexus file resulting from Phylomatic List of taxa and presence or absence of adaptogenic

trait with 0/1 codes added........................................................................................................... 120

8. Tree resulting from TreeView with adaptogenic species bolded ............................................ 126


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ABSTRACT

The contribution of plants to pharmacology has been estimated in the billions of dollars over the past

twenty years. In particular, the development of pathological disorders related to heightened stress

sensitivity and dysregulation of stress-coping mechanisms is of great concern today. Modern medicine is

in need of novel remedies that can treat conditions resulting from dysfunctional stress response. An

obscure pharmacological class of medicinal plants called adaptogens suggests novel strategies for treating

stress-related disorders. Adaptogens have been shown to increase resistance to a wide variety of stressors

and are further defined by three criteria. They must: cause minimal disturbance to the normal physiological

function of an organism, increase resistance to a wide range of stressors, and have a normalizing action

irrespective of the direction of the preceding pathological changes.

The recent phylogenetic restructuring of angiosperm plant families due to modern DNA techniques

affords the opportunity to place plant species with similar pharmacological properties on the tree of life. I

hypothesize that by determining the phylogenetic relationships of plant species with adaptogenic activity,we can begin to search for other potentially adaptogenic plant species that are presently unknown. This

study involves the phylogenetic placement of adaptogenic angiosperm species on the Angiosperm

Phylogeny Group megatree which was derived from national data sources.A thorough search of the literature resulted in a list of 183 candidate species representing all major

subgroups of angiosperms. From this list 33 species were identified with potential adaptogenic properties.

The resulting phylogenetic tree shows both independent evolution and clustering at the species level, and in

one case, a subtribe. This erratic distribution may be due to the highly variable nature of secondary

metabolites responsible for the adaptogenic response. The systematic value of the adaptogenic trait is open

to interpretation in that absence of the trait could be due to loss or to switched off gene expression. Despite

the seemingly high degree of independent evolution of adaptogenic properties at higher taxonomic levels,

targeting closely related species should prove very worthwhile for increasing the sources of adaptogenic

plant species.

Robyn Klein 2006 www.rrreading.com

Phylogenetic and phytochemical characteristics of plant species with adaptogenic propertiesMS Thesis, 2004, Montana State University

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phylogenetic and phytochemical characteristics abstract klein

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